Browsing by Author "Pal, Sumanta K"

Now showing 1 - 3 of 3
  • Thumbnail Image
    ItemOpen Access
    Active surveillance of metastatic renal cell carcinoma: Results from a prospective observational study (MaRCC).
    (Cancer, 2021-07) Harrison, Michael R; Costello, Brian A; Bhavsar, Nrupen A; Vaishampayan, Ulka; Pal, Sumanta K; Zakharia, Yousef; Jim, Heather SL; Fishman, Mayer N; Molina, Ana M; Kyriakopoulos, Christos E; Tsao, Che-Kai; Appleman, Leonard J; Gartrell, Benjamin A; Hussain, Arif; Stadler, Walter M; Agarwal, Neeraj; Pachynski, Russell K; Hutson, Thomas E; Hammers, Hans J; Ryan, Christopher W; Inman, Brant A; Mardekian, Jack; Borham, Azah; George, Daniel J

    Background

    Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature.

    Methods

    This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival.

    Results

    Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST.

    Conclusions

    AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.
  • Thumbnail Image
    ItemOpen Access
    Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond.
    (J Immunother Cancer, 2018-01-25) Zhu, Jason; Armstrong, Andrew J; Friedlander, Terence W; Kim, Won; Pal, Sumanta K; George, Daniel J; Zhang, Tian
    Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility. Further limitations include the use of archival specimens to measure this dynamic biomarker. Indeed, until PD-L1 testing is standardized and can consistently predict treatment outcome, the currently available PD-L1 assays are not clinically useful in urothelial and renal cell carcinoma. Other more promising biomarkers include tumor mutational burden, profiles of tumor infiltrating lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker may be best but will need prospective testing to validate such a biomarker.
  • Thumbnail Image
    ItemOpen Access
    Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma.
    (Journal for immunotherapy of cancer, 2018-01-29) Koshkin, Vadim S; Barata, Pedro C; Zhang, Tian; George, Daniel J; Atkins, Michael B; Kelly, William J; Vogelzang, Nicholas J; Pal, Sumanta K; Hsu, JoAnn; Appleman, Leonard J; Ornstein, Moshe C; Gilligan, Timothy; Grivas, Petros; Garcia, Jorge A; Rini, Brian I
    Nivolumab is approved for patients with metastatic renal cell carcinoma (mRCC) refractory to prior antiangiogenic therapy. The clinical activity of nivolumab in patients with non-clear cell RCC subtypes remains unknown as these patients were excluded from the original nivolumab trials.Patients from 6 centers in the United States who received at least one dose of nivolumab for non-clear cell mRCC between 12/2015 and 06/2017 were identified. A retrospective analysis including patient characteristics, objective response rate according to RECIST v1.1 and treatment-related adverse events (TRAEs) was undertaken.Forty-one patients were identified. Median age was 58 years (33-82), 71% were male, and majority had ECOG PS 0 (40%) or 1 (47%). Histology included 16 papillary, 14 unclassified, 5 chromophobe, 4 collecting duct, 1 Xp11 translocation and 1 MTSCC (mucinous tubular and spindle cell carcinoma). Among 35 patients who were evaluable for best response, 7 (20%) had PR and 10 (29%) had SD. Responses were observed in unclassified, papillary and collecting duct subtypes. In the entire cohort, median follow-up was 8.5 months and median treatment duration was 3.0 months. Median PFS was 3.5 months and median OS was not reached. Among responders, median time to best response was 5.1 months, and median duration of response was not reached as only 2 out of 7 responders had disease progression during follow-up. TRAEs of any grade were noted in 37% and most commonly included fatigue (12%), fever (10%) and rash (10%). Nivolumab treatments were postponed in 34% and discontinued in 15% of patients due to intolerance. No treatment-related deaths were observed.Nivolumab monotherapy demonstrated objective responses and was well tolerated in a heterogeneous population of patients with non-clear cell mRCC. In the absence of other data in this treatment setting, this study lends support to the use of nivolumab for patients with metastatic non-clear cell renal cell carcinoma.